Phytomedicine最新文献

{"title":"GelMA@APPA microspheres promote chondrocyte regeneration and alleviate osteoarthritis via Fgfr2 activation.","authors":"Jiakai Wang, Tao Sun, Rong Zhang, Tingting Wang, Yishuo Li","doi":"10.1016/j.phymed.2024.156176","DOIUrl":"10.1016/j.phymed.2024.156176","url":null,"abstract":"<p><strong>Background: </strong>In the context of osteoarthritis (OA), a condition marked by joint degeneration, there is a notable absence of efficacious approaches to promote regenerative healing in chondrocytes. Novel therapeutic strategies like nanomicelles-hydrogel microspheres loaded with Astragalus polysaccharide (GelMA@APPA) offer promising avenues for promoting chondrocyte regeneration and mitigating OA progression.</p><p><strong>Methods: </strong>Astragalus polysaccharide (APS) has been shown to induce chondrocyte proliferation and promote cartilage matrix secretion, demonstrating biological activity associated with chondrocyte regeneration. However, the clinical efficacy of APS remains uncertain. Therefore, this investigation validated the beneficial impact of APS on reducing knee joint damage severity induced by destabilization of the medial meniscus (DMM) in mice. The application of bioinformatics analysis and in vitro experimentation revealed that fibroblast growth factor receptor 2 (Fgfr2) in chondrocytes is a key target protein for APS in ameliorating OA-induced cartilage injury, as the deletion of chondrocyte Fgfr2 resulted in the complete loss of the therapeutic effect of APS. To enhance the efficacy of APS, we incorporated APS into nanoparticle-laden hydrogel microspheres to further bolster its potential in chondrocyte regeneration therapy. Subsequently, we developed GelMA@APPA, which exhibited no significant cytotoxic effects on normal chondrocytes in vitro and could be efficiently internalized by chondrocytes. Following subsequent in vitro and in vivo experiments, we affirmed the beneficial effects of GelMA@APPA on OA mice and cartilage cells damaged by OA, as well as its enhancement of the therapeutic effects of APS.</p><p><strong>Results: </strong>APS significantly improved knee joint injuries in OA mice. Bioinformatics and in vitro analyses identified Fgfr2 as a critical target protein for APS's regenerative effects. Disruption of Fgfr2 negated APS's benefits. GelMA@APPA demonstrated good biocompatibility, effective internalization by chondrocytes, and enhanced the therapeutic efficacy of APS in experiments conducted both in vitro and in vivo, improving chondrocyte proliferation and reducing apoptosis.</p><p><strong>Conclusions: </strong>This study demonstrates that GelMA@APPA microspheres effectively promote chondrocyte regeneration and OA treatment by activating Fgfr2. These findings suggest a novel therapeutic mechanism for OA and lay the groundwork for future clinical utilization of GelMA@APPA in regenerative medicine.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"137 ","pages":"156176"},"PeriodicalIF":6.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142953667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Shenghui decoction inhibits neuronal cell apoptosis to improve Alzheimer's disease through the PDE4B/cAMP/CREB signaling pathway.","authors":"Gai Gao, Xiaowei Zhang, Zhenghao Cui, Mingyue Fan, Yibing Yan, Yanli Huang, Yiting Shi, Huifen Ma, Zhenzhen Wang, Yunfang Su, Zhenqiang Zhang, Zhishen Xie","doi":"10.1016/j.phymed.2025.156366","DOIUrl":"10.1016/j.phymed.2025.156366","url":null,"abstract":"<p><strong>Background: </strong>Shenghui Decoction (SHD) is a frequently utilized traditional Chinese medicine formula in clinical settings for addressing cognitive impairment in elderly individuals. Nevertheless, the precise mechanism by which SHD exerts its effects on the most prevalent form of dementia, Alzheimer's disease (AD), remains to be elucidated.</p><p><strong>Methods: </strong>Temperature-induced transgenic C. elegans assess Aβ deposition and toxicity. Behavioral experiments are utilized to assess learning and memory capabilities as well as cognitive impairment in APP/PS1 mice. Immunofluorescence and immunohistochemistry are employed to identify Aβ deposits, while UHPLCOE/MS combine network pharmacology is utilized to characterize chemical composition, predict target and analyze the biological processes and signaling pathways modulated by SHD. Molecular biology methodologies confirm the functionality of regulatory pathways. Molecular docking, molecular dynamic simulations (MD) and ultrafiltration-liquid chromatography/mass spectrometry (LC/MS) are employed for the assessment of the binding interactions between active ingredients of SHD and target proteins.</p><p><strong>Results: </strong>SHD effectively reduced the deposition of Aβ in the head of C. elegans and mitigated its toxicity, as well as improved the learning deficits and cognitive impairment in APP/PS1 mice. Network pharmacology analyses revealed that G protein-coupled receptors (GPCRs) and cell apoptosis are the primary biological processes modulated by SHD, with KEEG results indicating that SHD regulated the cAMP signaling pathway. Subsequent experimental investigations demonstrated that SHD attenuated the loss of neurons in APP/PS1 mice, upregulated the expression of anti-apoptotic protein Bcl-2 and downregulated the expression of pro-apoptotic proteins like cleave-Caspase-3 both in vivo and in vitro. Additionally, SHD decreased intracellular AMP levels while increasing cAMP levels, leading to the phosphorylation of PKA to activate CREB. This process ultimately regulated the expression of Bcl-2, Bdnf, among others, to prevent cell apoptosis and safeguard neurons. Molecular docking, MD, and ultrafiltration-LC/MS revealed that the active constituents of SHD formed stable interactions with the cAMP hydrolysis enzyme phosphodiesterase 4B (PDE4B).</p><p><strong>Conclusion: </strong>SHD regulated the cAMP/CREB signaling pathway to inhibit neuronal cell apoptosis and improve AD. Furthermore, it is worth noting that this mechanism may be associated with the specific and consistent binding of SHD active ingredients to PDE4B, potentially offering promising candidates for drug development aimed at addressing AD.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"137 ","pages":"156366"},"PeriodicalIF":6.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142953704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integration of transcriptomics and metabolomics reveals the mechanism of Glycyrrhizae Radix Et Rhizoma extract inhibiting CCL5 in the treatment of acute pharyngitis.","authors":"Xiaoxiao Han, Chengtao Sun, Huizhe Ding, Shengqian Deng, Man Li, Jiayi Lou, Xipeng Song, Guoyin Kai","doi":"10.1016/j.phymed.2024.156360","DOIUrl":"10.1016/j.phymed.2024.156360","url":null,"abstract":"<p><strong>Background: </strong>Acute pharyngitis (AP) is a common condition marked by inflammation of the oropharynx, which can lead to severe throat swelling, breathing difficulties, and even suffocation, significantly impacting quality of life. Despite the beneficial anti-inflammatory activity of Glycyrrhizae Radix Et Rhizoma (GRER) and Isoliquiritigenin (ISL), their pharmacological mechanisms against AP remain unclear.</p><p><strong>Purpose: </strong>This study explores the mechanisms by which GRER treats AP, utilizing both transcriptomics and metabolomics approaches.</p><p><strong>Methods: </strong>We identified the chemical components of GRER and those that enter the bloodstream using UPLC-MS/MS. Based on15 % ammonia-induced AP model, this study integrates transcriptomics and metabolomics to investigate the mechanism of GRER and ISL in the AP treatment.</p><p><strong>Results: </strong>The results indicated that GRER has significantly protective and anti-inflammatory effects against AP. Our analysis identified 144 components of GRER in vitro and 17 components in vivo. Network pharmacology and quantitative analysis highlighted ISL as a key active ingredient responsible for GRER's anti-AP effects. Transcriptomics and metabolomics results indicate that GRER and its active ingredient ISL exert therapeutic effects on AP by inhibiting the expression of CCL5 in pharyngeal tissue, thereby downregulating the levels of pro-inflammatory metabolites malic acid and fumaric acid in the tricarboxylic acid (TCA) cycle pathway.</p><p><strong>Conclusion: </strong>The data in this article demonstrated that GRER and ISL has significantly anti-inflammatory effects and protective effects for AP by regulating CCL5 expression to reduce the levels of pro-inflammatory metabolites within TCA cycle pathway. It provides a scientific basis for prevention and treatment of AP.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"137 ","pages":"156360"},"PeriodicalIF":6.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"1,8-Cineole reduces pulmonary vascular remodelling in pulmonary arterial hypertension by restoring intercellular communication and inhibiting angiogenesis.","authors":"Jorge M Alves-Silva, Mónica Zuzarte, Carla Marques, Teresa Rodrigues, Júlia Barbeitos, Rui Caetano, Rui Baptista, Lígia Salgueiro, Henrique Girão","doi":"10.1016/j.phymed.2024.156334","DOIUrl":"10.1016/j.phymed.2024.156334","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary Arterial Hypertension (PAH) is characterized by pulmonary vascular remodelling, often associated with disruption of BMPR2/Smad1/5 and BMPR2/PPAR-γ signalling pathways that ultimately lead to right ventricle failure. Disruption of intercellular junctions and communication and a pro-angiogenic environment are also characteristic features of PAH. Although, current therapies improve pulmonary vascular tone, they fail to tackle other key pathological features that could prevent disease progression. In this scenario, aromatic plants emerge as promising sources of bioactive compounds, with 1,8-cineole standing out due to its hypotensive properties and cardioprotective effect in PAH.</p><p><strong>Purpose: </strong>The present study aims to explore for the first time the effect of 1,8-cineole in pulmonary vascular remodelling associated with PAH.</p><p><strong>Methods: </strong>Resorting to the monocrotaline (MCT)-induced PAH animal model, the effect of 1,8-cineole on vascular remodelling including interstitial collagen accumulation, smooth muscle cell proliferation and protein levels of BMPR2 pathway-related proteins, was assessed by microscopy and western blot (WB) analysis. The integrity of gap junctions, pulmonary surfactant, mitochondrial structure and endothelial cell barrier were evaluated by transmission electron microscopy, confocal microscopy and WB analysis. Furthermore, the effect of 1,8-cineole on angiogenesis was determined on pulmonary artery endothelial cells (PAEC) submitted to hypoxia using the scratch wound and Matrigel angiogenesis assays, and the number of sprouts on isolated healthy and diseased pulmonary artery rings, treated with the compound, enabled the validation of these effects.</p><p><strong>Results: </strong>1,8-Cineole mitigated PAH-associated derailment of both BMPR2/Smad1/5 and BMPR2/PPAR-γ pathways and concomitantly reduced interstitial fibrosis and the arterial medial layer thickness in pulmonary arteries. The compound restored gap junction, lung surfactant and mitochondrial integrity and preserved endothelial barrier integrity. Furthermore, 1,8-cineole exerted an anti-angiogenic effect, by impairing the formation of vessel-like structures in PAEC and sprouting formation in isolated pulmonary arteries.</p><p><strong>Conclusion: </strong>The present study brings new insights about the mechanisms whereby 1,8-cineole impacts pulmonary vascular remodelling and demonstrates the potential of 1,8-cineole as a therapeutic strategy to hamper PAH progression.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"137 ","pages":"156334"},"PeriodicalIF":6.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143010240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oral administration of Folium Artemisiae Argyi-derived exosome-like nanovesicles can improve ulcerative colitis by regulating intestinal microorganisms.","authors":"Yishu Li, Su Shao, Yuanhao Zhou, Yuanyuan Wang, Wenjie Zheng, Huanying Wang, Meixia Wang, Ketao Jin, Hai Zou, Xiaozhou Mou","doi":"10.1016/j.phymed.2025.156376","DOIUrl":"10.1016/j.phymed.2025.156376","url":null,"abstract":"<p><strong>Background: </strong>Ulcerative colitis (UC), an inflammatory disease characterized by intestinal barrier dysfunction, poses significant challenges because of the toxicity and adverse effects commonly associated with conventional therapies. Safer and more efficacious treatment strategies are needed.</p><p><strong>Purpose: </strong>The purpose of this study was to treat UC with Folium Artemisiae Argyi exosome-like nanovesicles (FAELNs) and to explore its related mechanism to provide a safer and more effective means for the treatment of ulcerative colitis.</p><p><strong>Methods: </strong>We established an in vivo model of acute UC in mice and an in vitro inflammatory model using HT-29 human colorectal cancer cells. To evaluate the therapeutic effect of FAELNs on UC, we adopted various proxies, including changes in body weight and disease activity index (DAI) of mice, and measurement of colon length. The concentrations of myeloperoxide, interleukin (IL-1β), IL-6, tumor necrosis factor-alpha, monocyte chemoattractant protein-1, and interferon-gamma in sera of mice were detected by ELISA. Immunohistochemistry, hematoxylin and eosin staining, and Alyssin blue staining were performed. The effect of HT-29 cells on oxidative stress was detected using an active oxygen probe, diacetyldichlorofluorescein, and flow cytometry. Western blotting was performed to detect the expression levels of Bax and Bcl-2 in HT-29 cells treated with FAELNs. The effects of FAELNs on IL-6 and IL-1β were detected by fluorescence quantitative PCR. Fecal 16S bacteria were detected, and the role of FAELNs was verified by α diversity and β diversity analyses, principal component analysis, species distribution, and function prediction. For microRNA sequencing of FAELNs, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed. To detect the metabolic and lipid groups of FAELNs, the components were identified and a pharmacological network was constructed to explore the related mechanisms and diseases.</p><p><strong>Results: </strong>FAELNs effectively alleviated the pathogenesis of UC induced by dextran sodium sulfate in animal models, restoring the integrity of the intestinal barrier and reversing an imbalance of the intestinal microbiota.</p><p><strong>Conclusion: </strong>Our findings demonstrate the therapeutic potential of FAELNs in UC management, highlighting their scalability for mass production and encouraging prospects for clinical transformation.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"137 ","pages":"156376"},"PeriodicalIF":6.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143010245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the interaction between calcium signaling and ferroptosis for novel cancer treatment.","authors":"Hao-Xin Yan, Yi-Zhong Zhang, Yu-Qing Niu, Yu-Wei Wang, Li-Hua Liu, Yu-Ping Tang, Ju-Min Huang, Elaine Lai-Han Leung","doi":"10.1016/j.phymed.2025.156377","DOIUrl":"10.1016/j.phymed.2025.156377","url":null,"abstract":"<p><strong>Background: </strong>Drug resistance in cancer is steadily rising, making the development of new therapeutic targets increasingly critical for improving treatment outcomes.</p><p><strong>Purpose: </strong>The mutual regulation of ions is essential for cell growth. Based on this concept, ion interference strategies offer a highly effective approach for cancer treatment. Calcium ions (Ca²⁺), as major second messengers, are closely associated with ion exchange and homeostasis. Disruptions in this balance can lead to cell death. However, while iron ions are also crucial, the connection between Ca²⁺and iron-induced cell death (ferroptosis) has not been well established. Therefore, this study suggests that Ca²⁺ may play a role in the induction of ferroptosis, presenting a novel and efficient target for cancer therapy.</p><p><strong>Study design: </strong>PubMed, Google Scholar, and Web of Science databases were systematically searched for articles published in the past 15 years on the mechanisms of calcium ion-induced ferroptosis in cancer and related drugs.</p><p><strong>Results: </strong>The analysis highlights how Ca²⁺regulate ferroptosis. The mechanisms by which Ca²⁺influence ferroptosis are summarized based on existing literature, and relevant drugs that act on Ca²⁺/ferroptosis axis are outlined.</p><p><strong>Conclusion: </strong>Ca²⁺ regulate ferroptosis primarily through the modulation of reactive oxygen species (ROS) and glutathione (GSH) levels, a mechanism that applies to a wide range of cancer cells as well as paracancerous and normal cells in cancer treatment. Furthermore, plant-derived active compounds exhibit potent anticancer properties and often act on the Ca²⁺/ferroptosis axis. These natural compounds could play a significant role in the development of new cancer treatment strategies.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"137 ","pages":"156377"},"PeriodicalIF":6.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Picrosides-rich fraction from Picrorhiza kurroa attenuates steatohepatitis in zebrafish and mice by modulating lipid metabolism and inflammation.","authors":"Swati Katoch, Jyoti Chhimwal, Damanpreet Singh, Dinesh Kumar, Vikram Patial","doi":"10.1016/j.phymed.2025.156368","DOIUrl":"10.1016/j.phymed.2025.156368","url":null,"abstract":"<p><strong>Background: </strong>Non-alcoholic steatohepatitis (NASH) has become a serious public health concern with high global prevalence. The lack of safe and efficient treatment for the condition demands exploring new therapeutic solutions.</p><p><strong>Purpose: </strong>In the present study, we investigated the protective efficacy of picrosides-rich fraction (PF) from Picrorhiza kurroa against steatohepatitis and revealed the molecular mechanism of action.</p><p><strong>Methods: </strong>PF was prepared and characterized using UPLC analysis. Initially, the efficacy of PF was studied on the zebrafish model of NASH. Further, a Methionine and Choline-Deficient (MCD) diet-induced NASH model in mice was employed to evaluate the hepatoprotective efficacy of PF by utilizing biochemical, histopathological and molecular studies.</p><p><strong>Results: </strong>The UPLC analysis revealed the presence of 29.11% and 29.86% picroside I and II in the PF, respectively. In the zebrafish model of NASH, PF treatment reduced the hepatic lipid accumulation and modulated the expressions of lipogenic, inflammatory, oxidative, and cellular stress genes. Further, in MCD diet-induced NASH in mice, PF treatment showed a significant improvement in body weights and serum liver injury markers. Reduced degenerative changes and fibrous tissue was observed in the PF-treated groups. The downregulated expression of Srebp1c, Cd36, Fas, Chrebp, Pparγ, and Hnf4α showed anti-lipogenic potential of PF treatment. NASH development followed oxidative stress, mitochondrial dysfunction, and inflammation in the liver of mice. However, PF treatment encouraged mitochondrial biogenesis by upregulating Pgc1α, Tfam, and Nrf2 expressions. The elevated levels of NFκB, TNFα, IL6, TGFβ, and αSMA were also restored by PF, advocating its anti-inflammatory and anti-fibrogenic effect.</p><p><strong>Conclusion: </strong>The present study revealed that PF ameliorate the progression of NASH by increasing mitochondrial biogenesis and decreasing lipogenesis, hepatic inflammation, and fibrosis.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"137 ","pages":"156368"},"PeriodicalIF":6.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143010246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergistic antimicrobial efficacy of glabrol and colistin through micelle-based co-delivery against multidrug-resistant bacterial pathogens.","authors":"Ying Liu, Mengying Zhang, Yawei Cai, Shuaicheng Wu, Chen Mei, Hongjun Wang, Shaoqi Qu","doi":"10.1016/j.phymed.2025.156371","DOIUrl":"10.1016/j.phymed.2025.156371","url":null,"abstract":"<p><strong>Background: </strong>Widespread bacterial infection and the spread of multidrug resistance (MDR) exhibit increasing threats to the public and thus require new antibacterial strategies. Coupled with the current slow pace of antibiotic development, the use of antibiotic adjuvants to revitalize existing antibiotics offers great potential.</p><p><strong>Purpose: </strong>We aim to explore the synergistic antimicrobial mechanism of glabrol (GLA) and colistin (COL) while developing an innovative multifunctional micelle-based drug delivery system to enhance therapeutic efficacy.</p><p><strong>Methods: </strong>The synergy between GLA and COL was assessed through a combination of high-throughput screening and checkerboard analysis techniques. Moreover, we performed fluorescence-based assays to investigate the underlying mechanisms of action of the GLA and COL combination. We also developed a multifunctional drug delivery platform that integrates GLA and COL into co-loaded composite micelles, aimed at improving antibacterial efficacy against peritoneal sepsis and chronic bacterial wound infections caused by diverse microbial pathogens.</p><p><strong>Results: </strong>We have discovered that natural flavonoids found in plants act synergistically with colistin against MDR bacterial infections, effectively improving its efficacy through a co-delivery strategy. The combination therapy consisting of GLA and COL exhibits enhanced antibacterial efficacy and is capable of clearing 99% of MDR Gram-positive and Gram-negative bacteria in 4 h. Mechanistic studies showed that COL increases the outer membrane permeability, which promotes the adhesion of GLA to the inner membrane, disrupting bacterial metabolism, and ultimately leading to bacterial death. Furthermore, a novel pH-responsive hydrogel system was developed and dispersed with GLA and COL co-loaded composite micelles to mitigate the selective pressure of antibiotics with fewer side effects. Lastly, such a system showed high efficacy in two animal models.</p><p><strong>Conclusion: </strong>Our findings provide a potential therapeutic option using a co-delivery system functionalized with combination therapy, to address the prevalent infections caused by complex bacterial infections and even MDR bacterial infections.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"137 ","pages":"156371"},"PeriodicalIF":6.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142953795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stigmasterol from Prunella vulgaris L. Alleviates LPS-induced mammary gland injury by inhibiting inflammation and ferroptosis.","authors":"Mingyang Sun, Dianwen Xu, Dianfeng Liu, Xin Ran, Feng Li, Jiaxin Wang, Yusong Ge, Yuhao Liu, Wenjin Guo, Juxiong Liu, Yu Cao, Shoupeng Fu","doi":"10.1016/j.phymed.2025.156362","DOIUrl":"10.1016/j.phymed.2025.156362","url":null,"abstract":"<p><strong>Background: </strong>Dairy mastitis, a prevalent condition affecting dairy cattle, represents a significant challenge to both animal welfare and the quality of dairy products. However, current treatment options remain limited. Stigmasterol (ST) is a bioactive component of Prunella vulgaris L. (PV) with various pharmacological functions such as anti-inflammatory and anti-oxidation. At present, the specific effects and underlying mechanisms of PV and ST on dairy mastitis are still not fully understood.</p><p><strong>Purpose: </strong>The aim of this research was to evaluate the pharmacological effects of PV and its active component ST on lipopolysaccharide (LPS) -stimulated bovine mammary epithelial cells (BMECs) and a mouse mastitis model, and to elucidate the possible mechanisms of action.</p><p><strong>Methods: </strong>UPLC-Q-TOF-MS/MS was employed to identify the constituents of PV. BMECs and mice were used to establish in vitro and in vivo models of mastitis. Western Blotting, RT-qPCR, immunofluorescence and other techniques were used to explore the effects of PV and ST on inflammatory factors, blood-milk barrier integrity, ferroptosis related indicators and their potential molecular mechanisms.</p><p><strong>Results: </strong>PV significantly attenuated the production of inflammatory mediators by LPS-stimulated BMECs. Subsequently, ST was found to be a potent anti-inflammatory agent in PV by inhibiting TLR4/NF-κB signaling pathway. This inhibition inhibits the myosin light chain (MLC)/MLC kinase signaling cascade and alleviates blood-milk barrier (BMB) disruption in BMECs. In addition, ferroptosis occurred in BMECs after LPS stimulation, and ST inhibited ferroptosis by stimulating Nrf2/GPX4 signaling pathway. Treatment of BMECs with the Nrf2 inhibitor ML385 significantly attenuated the therapeutic effect of ST. In vivo experiments further confirmed that both PV and ST attenuated LPS-induced breast tissue damage while reducing ferroptosis levels and restoring BMB.</p><p><strong>Conclusion: </strong>ST from PV exhibits substantial anti-inflammatory properties and is a promising candidate for the treatment of dairy mastitis.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"137 ","pages":"156362"},"PeriodicalIF":6.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"mTOR/HIF-1α pathway-mediated glucose reprogramming and macrophage polarization by Sini decoction plus ginseng soup in ALF.","authors":"Junli Zhang, Liyuan Hao, Shenghao Li, Ying He, Yang Zhang, Na Li, Xiaoyu Hu","doi":"10.1016/j.phymed.2025.156374","DOIUrl":"10.1016/j.phymed.2025.156374","url":null,"abstract":"<p><strong>Background: </strong>Acute liver failure (ALF) has a high mortality rate, and despite treatment advancements, long-term outcomes remain poor.</p><p><strong>Purpose: </strong>This study explores the therapeutic targets and pathways of Sini Decoction plus Ginseng Soup (SNRS) in ALF using bioinformatics and network pharmacology, focusing on its impact on macrophage polarization through glucose metabolism reprogramming. The efficacy of SNRS was validated in an LPS/D-GalN-induced ALF model, and its optimal concentration was determined for in vitro macrophage intervention.</p><p><strong>Study design and methods: </strong>Differentially expressed genes (DEGs) in HBV-induced and acetaminophen-induced ALF were identified from GEO datasets. The correlation between target gene expression and immune cell infiltration in ALF liver tissue was analyzed. AST, ALT, TNF-α, HMGB1, IL-1β, IL-6, and IL-10 levels were measured, and liver histopathology was assessed. Macrophage polarization was analyzed via immunofluorescence, flow cytometry, and Western blot. Glycolysis-related enzymes and metabolites, including HK2, PFK-1, PKM2, and LDHA, were quantified. Cellular ultrastructure was examined by transmission electron microscopy.</p><p><strong>Results: </strong>Five key glycolysis-regulating genes (HK2, CDK1, SOD1, VEGFA, GOT1) were identified, with significant involvement in the HIF-1 signaling pathway. Immune infiltration was markedly higher in ALF liver tissue. SNRS improved survival, reduced ALT/AST levels, alleviated liver injury, and modulated macrophage polarization by decreasing CD86 and increasing CD163 expression. In vitro, SNRS inhibited LPS-induced inflammatory cytokine release, lactate production, p-mTOR/mTOR ratio, and HIF-1α expression.</p><p><strong>Conclusion: </strong>SNRS modulates macrophage polarization and glucose metabolism reprogramming via the mTOR/HIF-1α pathway, showing promise as a treatment for ALF.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"137 ","pages":"156374"},"PeriodicalIF":6.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}